Field of the Invention
This invention relates to novel substituted amides and processes for their preparation. These compounds inhibit the action of the hormone angiotensin II (AII) and are therefore useful in alleviating angiotensin induced hypertension. AII is the product of two enzymes, renin and angiotensin converting enzyme, acting on angiotensinogen and angiotensin I, respectively. This peptide hormone is a powerful vasopressor which has been implicated as a causative agent for producing high blood pressure in various mammalian species, such as the rat, dog, and man. The compounds of this invention block the action of AII at its receptors on target cells and thus prevent the increase in blood pressure produced by the hormone-receptor interaction. By administering a compound of this invention to a species of mammal with hypertension due to AII, the blood pressure is reduced.
Carini, et al. in EP 0 324 377 issued Aug. 29, 1989 discloses 1,2,4-trisubstituted imidazoles of the formula: ##STR2## wherein R.sup.1 is carboxylic acid or a suitable isostere; R.sup.6 is lower alkyl, R.sup.7 is alkyl; perfluoroalkyl, or aryl; and R.sup.8 is hydroxymethyl, aldehyde, or carboxylic acid. These compounds block the action of AII on its receptor and do lower blood pressure.
Applicants have discovered that appropriately substituted amides are antagonists for the action of AII on its receptor similar to the imidazoles described in EP 0 324 377. Such compounds are not only interesting from a chemical viewpoint, but they also have pharmacological and medical utilities. Although many tertiary amides are known, these amides substituted as described below have not been disclosed previously.